apitegromab   Click here for help

GtoPdb Ligand ID: 11180

Synonyms: SRK-015 | SRK015
Compound class: Antibody
Comment: Apitegromab (SRK-015) is an anti-myoststin (GDF8) monoclonal antibody that is being developed by Scholar Rock [2]. Antagonism of myostatin's inhibitory effect on skeletal muscle mass is being predicted to combat muscle atrophy that is observed in patients with the neuromuscular degenerative disease spinal muscular atrophy (SMA). SRK-015 binds to promyostatin and latent myostatin in both serum and muscle [1]. In a mouse SMA model, a precursor of SRK-015 (muSRK-015P) increased muscle mass and function, which is indicative of therapeutic potential.

The primary defect in SMA occurs in defective production of survival motor neuron (SMN) protein and there are already approved drugs that are designed to promote production of functional SMN. Each drug uses a different mechanism to achieve this effect: Roche's Evrysdi® (risdiplam) is a SNM-2 splicing modifier, Biogen's Spinraza® (nusinersen) is an antisense oligonucleotide and Novartis have their gene therapy Zolgensma® (onasemnogene abeparvovec). Myostatin inhibition is likely to be considered as an adjunct to these existing therapies.

Peptide sequences submitted for the INN match patened sequences that are claimed in Scholar Rock's patent WO2017120523A4, and refer to a humanized IgG4 monoclonal referred to as Ab2 in the patent [1].
No information available.
Summary of Clinical Use Click here for help
SRK-015 has progressed to clinical trial in children with types 2 and 3 SMA. In addition the FDA has issued both orphan drug designation and rare pediatric disease designation for the use of SRK-015 in infants with SMA . The European Commission (EC) has also granted orphan medicinal product designation (December 2018).
Clinical Trials
Clinical Trial ID Title Type Source Comment References
NCT03921528 An Active Treatment Study of SRK-015 in Patients With Type 2 or Type 3 Spinal Muscular Atrophy Phase 2 Interventional Scholar Rock, Inc. This study is known as the TOPAZ trial. Interim efficacy and safety data (6-months) is expected in the fourth quarter of 2020, with top-line data for the 12-month treatment period due in the first half of 2021.